Previous studies of fibrinogen by electron microscopy have resulted in a confusing array of contradictory models. We have recently been able to demonstrate a consistent structure, a trinodular rod, in both shadowed and negatively stained specimens (Appendix A). This work establishes the overall structure of the molecule and sets the stage for a more extensive investigation by electron microscopy of the structure and polymerization of fibrinogen. Our immediate goal is to map the location of particular known parts of the three different polypeptide chains in the trinodular structure. We propose to prepare antibodies to specific small fragments of the fibrinogen molecule, such as the fibrinopeptide A, and to use these as probes to label the corresponding antigenic site on the fibrinogen molecule. The antibody label can be seen and located to a resolution of 2-3 nm in negatively stained specimens. We will also determine the location of the antigenic sites in fibrin polymers, using in this case a Fab fragment as a label and the computer image reconstruction system to locate the label relative to the 23 nm banding pattern. We will also determine the structure of large fragments from plasmin digestion, imaging these directly by the same techniques we used for intact fibrinogen. In the case of fragments which bind to fibrin monomer we will determine the location of the binding site on the trinodular structure. Any such site should be important in the polymerization reaction. Our results should be important at two levels. The mapping of antigenic sites on individual molecules will serve as a basis for collating the wealth of biochemical data into a definitive structural model. The mapping of these sites in the fibrin polymers should allow us to determine the arrangement of molecules and intermolecular contacts. These structural studies are an essential first step toward our ultimate goal: to understand the mechanism of the polymerization of fibrin.